Models of aerobic capacity and myocardial function: Possible association of cardiac myosin heavy chain ATPase

Aerobic running performance is used to assess cardiovascular function. Therefore, the goal of this study was to identify inbred rat strains that could serve as useful models for exploration of the genetic basis of aerobic endurance performance and cardiac function. Six rats of each gender from 11 different inbred strains were initially tested for: (1) maximal running capacity on a treadmill, and (2) isolated cardiac performance. Running performance was estimated from: (a) duration of the run, (b) distance run, and (c) vertical work performed. Cardiac output, during constant preload and afterload, was taken as a measure of cardiac performance from an isolated working heart preparation. Across the 11 strains, the distance run correlated positively with isolated cardiac performance (r = 0.87). Although the COP rats ran the shortest distance, cardiac output from the DA and BUF rat strains showed the widest divergence. Therefore, the following hypotheses were tested: (1) running capacity and cardiac function are reproducible phenotypes for these two inbred strains and (2) the differences in capacity are explained partly by variation in myosin heavy chain (MHC) ATPase activity. The DA rats ran 147% further than the BUF rats at exhaustion. Isolated myocardial contractility averaged 126 mul/beat in BUF rats compared to 202 mul/beat in DA rats (63% Delta) and correlated (r = 0.91) with running capacity. MHC ATPase obtained from DA left ventricles hydrolyzed ATP 64% faster than ATPase obtained from BUF rats; these differences were not due to the presence of beta-MHC isoform in either strain. These data demonstrate that these phenotypes are reproducible and that differences in aerobic capacity between BUF and DA rats can be partly explained by variation in ventricular alpha-MHC ATPase activity.